During recent years it has become generally accepted that adequate function of the human immune system depends on the complex interaction of the microbiota with the human mucosa (Belkaid et al., 2014; Cao et al., 2014). In normal health, nonpathogenic bacteria activate the immune system to induce tolerance to microbiota essential for energy harvesting and immune development (de Kivit et al., 2014; Geuking et al., 2014; Walker et al., 2014). However, under specific conditions immune responses may occur against microbes that contribute to the development of diseases such as IBD (Meijerink et al., 2010). Human health may benefit from more insight in how microorganisms contribute to homeostasis of immune responses and how they prevent inflammation. The hope is it will lead to design of tailored interventions.
Commensal Lactobacilli species may play an active role in the maintenance of homeostasis of immune responses by guiding the polarization of T-cells toward regulatory T (Treg) cells and suppression of allergy associated Th2 responses (Smelt et al., 2013). This is considered to be accomplished by the interactions of bacterial cell wall components or secreted bacterial products that interact with immune or epithelial cells in the human mucosa (Walker et al., 2014). These interactions however seem to contribute to more than just tolerance to the beneficial microbes. In many studies Lactobacilli have been shown to have a positive impact on immune responses as shown in several vaccination studies (Meijerink et al., 2012; Wells et al., 2011). Also, Lactobacilli activate more general tolerogenic cellular pathways in humans as recently shown (van Baarlen et al., 2010; van Baarlen et al., 2009).
Lactobacilli plantarum is a well characterized food-derived bacterium (van Baarlen et al., 2009). In previous studies it has been shown that Lactobacilli plantarum strains have different effects on human dendritic cells and human peripheral blood mononuclear cells (Meijerink et al., 2010; Meijerink et al., 2012; Wells et al., 2011; van Baarlen et al., 2010; van Baarlen et al., 2009; Van Hemert et al., 2010). By applying comparative genome hybridization a number of bacteriocins and cell-wall components involved in glycosylation of cell wall teichoic acids have been identified that are associated with these differential effects (Meijerink et al., 2010; Meijerink et al., 2012; Wells et al., 2011; van Baarlen et al., 2010; van Baarlen et al., 2009; Van Hemert et al., 2010; Smet et al., 2013). It is assumed that this differential expression of Lactobacilli plantarum genes contributes to the observed differences in activation of Toll-like receptor (TLR)2-4, CD14 antigens, and nucleotide-binding oligomerization domain-containing 2 (NOD2) (Meijerink et al., 2010). As a consequence of differences in TLR-binding, Lactobacillus plantarum strains induce upon incubation with monocytes or dendritic cells different quantities of the proinflammatory cytokine IL12 and the regulatory cytokine IL10 (Meijerink et al., 2010; Meijerink et al., 2012; Wells et al., 2011; van Baarlen et al., 2010; van Baarlen et al., 2009; Van Hemert et al., 2010; Smet et al., 2013; Smelt et al., 2013). The gastrointestinal barrier may be disrupted on almost a daily basis by e.g. nonsteroidal anti-inflammatory drugs (NAISDs), sports or alcohol intake and as such cause (mild) inflammation of the intestine. A mild stressor cytokine that is very common in the Western society is the consumption of an NSAID such as indomethacin. Millions are using NSAIDs for the treatment of musculoskeletal pain. A side effect of these NSAIDs is the mild inflammation of the intestine by disruption of the gastrointestinal immune barrier (Schoultz et al., 2012). As NSAIDs are used by millions worldwide there is an urgent need to treat such (mild) inflammation of the intestine.
Another issue where food derived antigens may play a role is in maintaining vaccination efficacy. It is well known that immune memory to an antigen encountered in past (some decades ago) may wane over time. When the individual encounters the antigen or pathogen associated with the antigen again, such waned immune memory may result in an insufficient response to the antigen or pathogen associated with the antigen (Deasy et al., 2013; Kerneis et al., 2014; Poorolajal et al., 2010; Schure et al., 2012).
Accordingly, there is an urgent need to preserve, maintain and/or reactivate the immune memory. This could not only revive a waned immune response, it could also render the host immune system more susceptible to vaccination protocols, which may be specifically beneficial for immune compromised individuals such as elderly. In addition, to identify and to demonstrate effects of immune modulating products, adequate biomarkers and assays are lacking. Accordingly, there is an urgent need for such biomarker and/or assay.